Camp Nicola J, Cannon-Albright Lisa A, Farnham James M, Baffoe-Bonnie Agnes B, George Asha, Powell Isaac, Bailey-Wilson Joan E, Carpten John D, Giles Graham G, Hopper John L, Severi Gianluca, English Dallas R, Foulkes William D, Maehle Lovise, Moller Pal, Eeles Ros, Easton Douglas, Badzioch Michael D, Whittemore Alice S, Oakley-Girvan Ingrid, Hsieh Chih-Lin, Dimitrov Latchezar, Xu Jianfeng, Stanford Janet L, Johanneson Bo, Deutsch Kerry, McIntosh Laura, Ostrander Elaine A, Wiley Kathleen E, Isaacs Sarah D, Walsh Patrick C, Thibodeau Stephen N, McDonnell Shannon K, Hebbring Scott, Schaid Daniel J, Lange Ethan M, Cooney Kathleen A, Tammela Teuvo L J, Schleutker Johanna, Paiss Thomas, Maier Christiane, Grönberg Henrik, Wiklund Fredrik, Emanuelsson Monica, Isaacs William B
University of Utah ICPCG Group and Division of Genetic Epidemiology, University of Utah School of Medicine, 391 Chipeta Way, Suite D, Salt Lake City, UT 84108, USA.
Hum Mol Genet. 2007 Jun 1;16(11):1271-8. doi: 10.1093/hmg/ddm075. Epub 2007 May 3.
Previously, an analysis of 14 extended, high-risk Utah pedigrees localized in the chromosome 22q linkage region to 3.2 Mb at 22q12.3-13.1 (flanked on each side by three recombinants) contained 31 annotated genes. In this large, multi-centered, collaborative study, we performed statistical recombinant mapping in 54 pedigrees selected to be informative for recombinant mapping from nine member groups of the International Consortium for Prostate Cancer Genetics (ICPCG). These 54 pedigrees included the 14 extended pedigrees from Utah and 40 pedigrees from eight other ICPCG member groups. The additional 40 pedigrees were selected from a total pool of 1213 such that each pedigree was required to contain both at least four prostate cancer (PRCA) cases and exhibit evidence for linkage to the chromosome 22q region. The recombinant events in these 40 independent pedigrees confirmed the previously proposed region. Further, when all 54 pedigrees were considered, the three-recombinant consensus region was narrowed down by more than a megabase to 2.2 Mb at chromosome 22q12.3 flanked by D22S281 and D22S683. This narrower region eliminated 20 annotated genes from that previously proposed, leaving only 11 genes. This region at 22q12.3 is the most consistently identified and smallest linkage region for PRCA. This collaborative study by the ICPCG illustrates the value of consortium efforts and the continued utility of linkage analysis using informative pedigrees to localize genes for complex diseases.
此前，对14个犹他州的高危扩展家系进行分析，将22号染色体连锁区域定位到22q12.3 - 13.1处的3.2 Mb（两侧各有三个重组体），该区域包含31个注释基因。在这项大型、多中心的合作研究中，我们对从国际前列腺癌遗传学联盟（ICPCG）的九个成员组中挑选出的54个家系进行了统计重组定位，这些家系对于重组定位具有信息价值。这54个家系包括来自犹他州的14个扩展家系以及来自ICPCG其他八个成员组的40个家系。另外40个家系是从总共1213个家系中挑选出来的，每个家系都要求至少包含四个前列腺癌（PRCA）病例，并显示出与22号染色体区域连锁的证据。这40个独立家系中的重组事件证实了先前提出的区域。此外，当考虑所有54个家系时，三个重组体的共识区域缩小了超过1兆碱基，至22号染色体q12.3处的2.2 Mb，两侧分别为D22S281和D22S683。这个更窄的区域从先前提出的区域中排除了20个注释基因，仅剩下11个基因。22q12.3处的这个区域是PRCA中最一致确定且最小的连锁区域。ICPCG的这项合作研究说明了联盟努力的价值以及使用信息丰富的家系进行连锁分析以定位复杂疾病基因的持续效用。
